SN5 SHORT NOTE 5M ★ High-yield

Describe the effects of hypoxia and ischaemia on the cell. Add a note on reperfusion injury.

Pathology · 2nd Professional — Para-Clinical

Definitions

Hypoxia is a deficiency of oxygen supply to a tissue. ischaemia is a reduction of blood flow, and so involves loss of substrate delivery and of waste removal as well.

Ischaemia injures a tissue faster and more severely than hypoxia alone, because anaerobic glycolysis cannot proceed without a supply of glucose either
Causes of hypoxia — ischaemic (reduced flow), anaemic (reduced carrying capacity), hypoxic (low inspired or arterial oxygen), and histotoxic (cyanide, which blocks cytochrome oxidase)

Sequence of Events

Loss of oxidative phosphorylation → ATP falls → Na+/K+ ATPase fails → sodium and water enter → cellular swelling — the earliest change → Anaerobic glycolysis → lactate accumulates → pH falls → clumping of nuclear chromatin → Ribosomes detach from the endoplasmic reticulum → protein synthesis falls → Calcium enters → activates phospholipases, proteases, endonucleases and ATPases → Mitochondrial permeability transition — the point of no return → Membrane rupture and lysosomal enzyme release → necrosis

Susceptibility of Tissues

Tissue	Tolerates ischaemia for
Neurones	3–5 minutes
Myocardium	20–30 minutes
Hepatocytes	1–2 hours
Skeletal muscle	2–3 hours
Fibroblasts	Many hours

Susceptibility follows metabolic rate — the more a tissue depends on oxidative phosphorylation, the less it tolerates ischaemia
This table dictates clinical urgency: "time is brain" in stroke and "time is muscle" in myocardial infarction are direct statements of it

Reperfusion Injury

Restoration of blood flow to ischaemic but still viable tissue paradoxically accelerates injury, so that the final damage exceeds what the ischaemia alone would have caused.

Mechanism	Explanation
Oxidative stress	Returning oxygen is converted to free radicals by damaged mitochondria and by infiltrating leucocytes
Calcium overload	Reperfusion delivers more calcium to cells whose pumps have already failed
Inflammation	Neutrophils arrive with the restored flow and release enzymes and radicals
Complement activation	IgM antibody deposits on ischaemic tissue and fixes complement

CLINICAL PEARL

Reperfusion injury is the price of successful revascularisation. Thrombolysis, angioplasty and bypass all save far more tissue than they damage — but this explains why myocardium is sometimes "stunned" after reperfusion, and why arrhythmia is commonest at the moment flow returns. It is not an argument against reperfusion, only for doing it early.

Applied Aspects

Myocardial infarction — irreversible injury begins at 20–30 minutes and is complete by about 6 hours; the whole rationale of "door to balloon time" is to salvage the ischaemic border zone
Cerebral ischaemia — the penumbra around an infarct is viable but non-functioning tissue that thrombolysis can save within a narrow window
Crush syndrome — reperfusion of crushed muscle releases potassium, myoglobin and phosphate, causing hyperkalaemic arrest and acute kidney injury
Ischaemic preconditioning — brief ischaemic episodes protect against a later prolonged one; an endogenous adaptation now being explored therapeutically
Organ preservation for transplantation uses cold and specialised solutions precisely to slow metabolism and limit these events

All questions in General Pathology: Cell Injury, Adaptation & Cell Death

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